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Gayle Nicholas Scott, PharmD DISCLOSURES October 26, 2015
"Herbal Pfizer’s Blue" has been in the news recently. Are these products safe and/or effective? Gayle Nicholas Scott, PharmD Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia
Remedies for male sexual enhancement have been available for millennia. The Ebers Papyrus, dating back to around 1600 BC, recommended topical application of baby crocodile hearts mixed with wood oil. A Sanskrit text written six centuries earlier suggested a man could visit 100 women after consuming a mixture of goat testes boiled in milk, sesame seeds, and the lard of a porpoise. Impotence, a nonspecific term that includes both erectile dysfunction and reduced libido, is clearly not a condition limited to modern civilization.
Erectile dysfunction affects an estimated18 million men in the United States, with a prevalence of 18.4% in men aged 20 years and older. Prevalence increases with age, ranging from 5% in men aged 20-39 years to 70% in men aged 70 years and older. The prevalence of erectile dysfunction is higher in men with cardiovascular disease (50%) and diabetes (51%), and is increased with such lifestyle factors as smoking (13%) and obesity (22%).
Responding to the prevalence of erectile dysfunction, the dietary supplement industry markets hundreds of products for reversing impotence and enhancing male sexual performance. Legally, dietary supplement labels cannot make medical claims, such as "for treatment of erectile dysfunction"; however, such claims as "to enhance sexual function" are permissible. An Internet search for "male sexual enhancement products" yielded more than 2 million hits, with websites offering products for purchase as well as information and testimonials.
Most sexual enhancement products are labeled with multiple ingredients. Commonly listed ingredients on male enhancement products include Butea superba (red kwao krua), Chlorophytum borivilianum (safed musli), Crocus sativus (saffron), dehydroepiandrosterone (DHEA), Epimedium grandiflorum (epimedium, horny goat weed), Eurycoma longifolia (tongkat ali, pasak bumi), Fadogia agrestis (fadogia), Ginkgo biloba, Lepidium meyenii (maca), Muira puama (potency wood), Panax ginseng, Pausinystalia yohimbe (yohimbe bark, not to be confused with the prescription drug yohimbine), Pinus pinaster (pycnogenol, pine bark), Serenoa repens (saw palmetto), Turnera aphrodisiaca (damiana), and Tribulus terrestris (devil's weed, goathead). Vitamins, minerals, and amino acids, such as L-arginine and propionyl L-carnitine, are frequent additions.
Many of these products have been studied only in male rats, but the few studies in men have been small or poorly designed, limiting conclusions about efficacy and safety.
Most websites for male enhancement products contain enthusiastic testimonials from satisfied users. But the question remains of whether these products really work, despite the dearth of clinical evidence supporting the efficacy of the ingredients.
Some products for sexual enhancement augment sexual activity, but the labeled ingredients may not be the source of the effect. Of the 232 drug recalls by the US Food and Drug Administration (FDA) between 2007 and 2012—all for unlabeled drug ingredients—51% were dietary supplements. Of the dietary supplement products recalled, sexual enhancement products were the most commonly recalled (40%), followed by bodybuilding (31%) and weight-loss products (27%). Of the 1560 Health Safety Alerts for dietary supplements issued by the FDA MedWatch and Health Canada between 2005 and 2013, 33% were for sexual enhancement products.
Unlabeled drugs in sexual enhancement products are frequently the prescription-only phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil (Pfizer’s Blue®), tadalafil (Cialis®), vardenafil (Levitra®), and avanafil (Stendra®). With increasing frequency, the unlabeled drugs may be analogues of PDE5 inhibitors that have been modified slightly from the parent structures. These derivatives are not detected by routine laboratory screening, which reduces the risk for both detection by the FDA and lawsuits for patent infringement.
To date, more than 50 unapproved analogues of prescription PDE5 inhibitors have been identified.
Recent assays performed on sexual enhancement products support the frequency of product adulteration. Of 91 products analyzed, 74 (81%) contained PDE5 inhibitors, including tadalafil and/or sildenafil (n = 40) or PDE5-inhibitor analogues (n = 34). Of the products containing prescription ingredients, 18 contained more than 110% of the highest approved drug product strength.
Another study of 150 sexual enhancement products (eg, Evil Root, Herbal Stud, Magic Sex, ULTRASize) found 61% of the products were adulterated with PDE5 inhibitors: 27% with sildenafil, tadalafil, or vardenafil, and 34% with similar structural analogues. Among the adulterated products, 64% contained only one PDE5 inhibitor and 36% contained mixtures of two to four PDE5 drugs or analogues. The amounts of PDE5 inhibitor prescription medicines were higher than the maximum recommended dose in 25% of products. Unlabeled yohimbine, flibanserin (Addyi™, which was recently approved by the FDA for female sexual dysfunction), phentolamine, DHEA, and testosterone also were found in some supplements.
Other researchers have found similarly adulterated products, many containing PDE5 inhibitor doses in excess of labeled amounts.
Although dietary supplements are marketed as "all natural" with implied safety, the available research suggests caution. A recent survey indicates that cardiac symptoms were a frequent cause of emergency department visits among men aged 20-39 years taking sexual enhancement products. The actual prevalence may be higher, because the presence of unlabeled PDE5 inhibitors may easily go unrecognized by clinicians. Common adverse effects of PDE5 inhibitors, such as flushing, lightheadedness, or dyspepsia, may be attributed to niacin and yohimbe, ingredients often found in sexual enhancement products. Profound hypoglycemia after ingestion of sexual enhancement products containing sildenafil and glyburide (Micronase® and others) also has been reported.
The covert addition of analogues of PDE5 inhibitors, which are not readily detectable by chemical screens, is particularly concerning. Although these chemical cousins of PDE5 inhibitors may retain the desired pharmacologic effect, none have been clinically tested for safety and toxicologic effects.
Obtaining dietary supplement products for sexual enhancement products has several perceived advantages. The purchase can be made discreetly, conveniently, and without a visit to a prescriber. Unlike drugs, dietary supplements are not required to be labeled with adverse effect or drug interaction information. Men taking prescription drugs, such as nitrates, may perceive dietary supplements for sexual enhancement as safe alternatives to contraindicated PDE5 inhibitors.
Clinicians should maintain a high degree of awareness for the potential for adverse effects of sexual enhancement products in men with unexplained cardiovascular symptoms. Patients who express interest in sexual enhancement supplements should be referred to their healthcare provider. Explain that even though a PDE5 inhibitor is not on the label, the supplement may have these ingredients added illegally without regard to patient safety. Patients should be warned of possible changes in vision and decreases in blood pressure, and the potentially dangerous combination of PDE5 inhibitors and nitrates that require medical advice. PDE5 inhibitors are substrates of cytochrome P450 3A4 (CYP3A4). Monitoring is required to avoid an interaction with CYP3A4 inhibitor drugs, such as erythromycin, which may result in high PDE5 levels.
In summary, advise patients that dietary supplements for sexual enhancement fall into one of two categories: those that might be safe but do not work, and those that might work but are not safe.
'Designer Vagina’ has become a term synonymous with vaginal cosmetic surgery in the media.
In these body-conscious times, the number of these kinds of surgeries has increased five times over the last decade. But with the NHS now only carrying out vaginal surgery in the most extreme of cases, what happens to the women who are turned down but still want to have it done?
We follow Antonia, whose confidence and relationships have suffered due to discomfort from her labia, as she attends a private clinic for vaginal surgery.
Part of a series of BBC Three programmes examining Extraordinary Bodies.
Feminism, by creating artificial scarcity of sexual resources, is responsible for much of the deadly infighting among men, as well as male suicides.
France's prime minister has raised the terrifying specter of ISIS carrying out chemical or biological weapons attacks on the West, but international investigators have so far confirmed only a single use of mustard gas by the terror gang in the Middle East.
The Organization for the Prohibition of Chemical Weapons, which enforces a global treaty, announced earlier this month that it had determined with "utmost confidence" that a "non-state actor" used the outlawed agent outside Aleppo, Syria, in August, likely killing a baby.
U.S. intelligence officials told NBC News that ISIS was the non-state actor. The OPCW is continuing to investigate other suspected uses of chemical weapons by ISIS.
ISIS trackers say its current arsenal includes weapons that are easily scavenged: mustard gas in Syria, which stockpiled hundreds of tons before agreeing to dispose of it two years ago, and chlorine that could be obtained from any water treatment facility in territory it has seized.
That seemed to be confirmed in a Tumblr post in August by high-profile ISIS fighter Israfil Yilmaz.
"It’s only acceptable when the regime or any other group uses chemical warfare against us?" he wrote.
"The regime uses chemical warfare on a regular basis these days, and nobody bats an eye — yet when IS captures it from them and uses it against them it’s all of a sudden a huge problem?
"Fight them the way they fight you."
The Associated Press reported Thursday that Iraqi and American intelligence officials believe ISIS is hell-bent on ramping up a chemical weapons program with help of scientists in the territory that forms its so-called caliphate.
An Iraqi politician, citing intelligence reports, told the AP that ISIS has recruited chemical experts Chechnya, Southeast Asia and Iraq, including some who once worked for Saddam Hussein. NBC News has not been able to confirm that assessment.
It's a nightmare scenario, as illustrated by French Prime Minister Manuel Valls' warning to Parliament that bullets and bombs could be replaced by something less tangible but just as deadly.
"We must not rule anything out," Valls said.
But intelligence officials in Washington caution that intent is a far cry from capability, particularly when it comes to more sophisticated weapons like nerve gas.
"We know they are pursuing chemical weapons, but we haven't seen anything beyond mustard and chlorine," said Patrick Martin, an Iraq expert with the Institute for the Study of War, a military research think tank in Washington.
He said that even with mustard gas, the damage has been limited because it's essentially just added to warheads and mortars.
"They don't deploy it on wide scales," Martin said. "Their delivery systems aren't that sophisticated."
But does ISIS have the ability to develop weapons that would pose a threat to the West going forward?
Martin said that's still unclear.
"Mosul [seized by ISIS in June] has a university and that theoretically has the lab facilities to deal with this. The difficulty they may face is in obtaining the raw materials," he said.
Retired Lt. Gen Richard Zahner, a former top military intelligence officer in Iraq, said that while al Qaeda was never able to launch a chemical weapons program, ISIS has greater financial resources.
"Even a few competent scientists and engineers, given the right motivation and a few material resources, can produce hazardous industrial and weapons-specific chemicals in limited quantities," he told the AP.
And the U.S. military has noted that ISIS has been able to lure scientists to its side. In January, U.S. Central Command announced that an airstrike had killed Abu Mailk, a chemical expert who had worked under Saddah Hussein.
"His death is expected to temporarily degrade and disrupt the terrorist network and diminish ISIL's (ISIS') ability to potentially produce and use chemical weapons against innocent people," the statement said.
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